Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancer

Abstract Introduction This study investigated whether programmed death‐ligand 1 (PD‐L1) expression of circulating tumor cells (CTCs) in peripheral blood can serve as a predictive biomarker for immunotherapy efficacy in patients with advanced non‐small‐cell lung cancer (NSCLC). Methods We employed a...

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Main Authors: Qing Zhou, Xiangning Liu, Ji Li, Bing Tong, Yan Xu, Minjiang Chen, Xiaoyan Liu, Xiaoxing Gao, Yuequan Shi, Jing Zhao, Wei Zhong, Mengzhao Wang
Format: Article
Language:English
Published: Wiley 2023-02-01
Series:Thoracic Cancer
Subjects:
Online Access:https://doi.org/10.1111/1759-7714.14767
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author Qing Zhou
Xiangning Liu
Ji Li
Bing Tong
Yan Xu
Minjiang Chen
Xiaoyan Liu
Xiaoxing Gao
Yuequan Shi
Jing Zhao
Wei Zhong
Mengzhao Wang
author_facet Qing Zhou
Xiangning Liu
Ji Li
Bing Tong
Yan Xu
Minjiang Chen
Xiaoyan Liu
Xiaoxing Gao
Yuequan Shi
Jing Zhao
Wei Zhong
Mengzhao Wang
author_sort Qing Zhou
collection DOAJ
description Abstract Introduction This study investigated whether programmed death‐ligand 1 (PD‐L1) expression of circulating tumor cells (CTCs) in peripheral blood can serve as a predictive biomarker for immunotherapy efficacy in patients with advanced non‐small‐cell lung cancer (NSCLC). Methods We employed a negative enrichment method to isolate CTCs. We identified PD‐L1 + CTCs as PD‐L1+/4′,6‐diamidino‐2‐phenylindole (DAPI)+/CD45‐circulating tumor cells through an immunofluorescence method. Tumor tissue PD‐L1 expression was determined by immunohistochemical staining. The correlation between CTC PD‐L1 expression and patients' prognostic features was estimated through the Kaplan–Meier method. Results CTCs released a higher detection rate of PD‐L1 expression than tumor tissues (53.0% vs. 42.1%). No correlation was observed between them. Forty‐nine NSCLC patients received anti‐PD‐1/PD‐L1 immunotherapy (three with combined anti‐PD‐1/PD‐L1 and cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4), two with four cycles of combined immune checkpoint inhibitors [ICIs] plus chemotherapy and ICI monotherapy for maintenance). Patients with PD‐L1 expression on tissue or CTCs had a median progression‐free survival (mPFS) of 5.6 months (n = 36, 95% confidence interval [CI] 3.6–7.5 months), significantly longer than those without PD‐L1 detection (n = 9, mPFS of 1.4 months, 95% CI 1.3–1.5 months, log‐rank p = 0.032). The multivariable Cox proportional‐hazard model suggested that the tissue or CTC PD‐L1 expression was associated with a lower risk of progression (hazard ratio 0.45, 95% CI 0.21–0.98, p = 0.043). Conclusions CTCs and tumor tissues reveal heterogeneous expression of PD‐L1 in NSCLC patients. Patients with baseline PD‐L1 expression on CTCs or tissue showed prolonged mPFS and may help to identify the subsets of patients who potentially benefit from immunotherapy.
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spelling doaj.art-33ac306df8ef419f88997f9415254a1d2023-02-14T02:01:34ZengWileyThoracic Cancer1759-77061759-77142023-02-0114547047810.1111/1759-7714.14767Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancerQing Zhou0Xiangning Liu1Ji Li2Bing Tong3Yan Xu4Minjiang Chen5Xiaoyan Liu6Xiaoxing Gao7Yuequan Shi8Jing Zhao9Wei Zhong10Mengzhao Wang11Department of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Pathology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaDepartment of Respiratory Medicine Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences Beijing ChinaAbstract Introduction This study investigated whether programmed death‐ligand 1 (PD‐L1) expression of circulating tumor cells (CTCs) in peripheral blood can serve as a predictive biomarker for immunotherapy efficacy in patients with advanced non‐small‐cell lung cancer (NSCLC). Methods We employed a negative enrichment method to isolate CTCs. We identified PD‐L1 + CTCs as PD‐L1+/4′,6‐diamidino‐2‐phenylindole (DAPI)+/CD45‐circulating tumor cells through an immunofluorescence method. Tumor tissue PD‐L1 expression was determined by immunohistochemical staining. The correlation between CTC PD‐L1 expression and patients' prognostic features was estimated through the Kaplan–Meier method. Results CTCs released a higher detection rate of PD‐L1 expression than tumor tissues (53.0% vs. 42.1%). No correlation was observed between them. Forty‐nine NSCLC patients received anti‐PD‐1/PD‐L1 immunotherapy (three with combined anti‐PD‐1/PD‐L1 and cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4), two with four cycles of combined immune checkpoint inhibitors [ICIs] plus chemotherapy and ICI monotherapy for maintenance). Patients with PD‐L1 expression on tissue or CTCs had a median progression‐free survival (mPFS) of 5.6 months (n = 36, 95% confidence interval [CI] 3.6–7.5 months), significantly longer than those without PD‐L1 detection (n = 9, mPFS of 1.4 months, 95% CI 1.3–1.5 months, log‐rank p = 0.032). The multivariable Cox proportional‐hazard model suggested that the tissue or CTC PD‐L1 expression was associated with a lower risk of progression (hazard ratio 0.45, 95% CI 0.21–0.98, p = 0.043). Conclusions CTCs and tumor tissues reveal heterogeneous expression of PD‐L1 in NSCLC patients. Patients with baseline PD‐L1 expression on CTCs or tissue showed prolonged mPFS and may help to identify the subsets of patients who potentially benefit from immunotherapy.https://doi.org/10.1111/1759-7714.14767circulating tumor cellsimmunotherapynon‐small‐cell lung cancerprogrammed death‐ligand 1
spellingShingle Qing Zhou
Xiangning Liu
Ji Li
Bing Tong
Yan Xu
Minjiang Chen
Xiaoyan Liu
Xiaoxing Gao
Yuequan Shi
Jing Zhao
Wei Zhong
Mengzhao Wang
Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancer
Thoracic Cancer
circulating tumor cells
immunotherapy
non‐small‐cell lung cancer
programmed death‐ligand 1
title Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancer
title_full Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancer
title_fullStr Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancer
title_full_unstemmed Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancer
title_short Circulating tumor cells PD‐L1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non‐small‐cell lung cancer
title_sort circulating tumor cells pd l1 expression detection and correlation of therapeutic efficacy of immune checkpoint inhibition in advanced non small cell lung cancer
topic circulating tumor cells
immunotherapy
non‐small‐cell lung cancer
programmed death‐ligand 1
url https://doi.org/10.1111/1759-7714.14767
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